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In llama crias (tekes), Escherichia coli and Staphylococcus aureus are major pathogens, and marbofloxacin could be a suitable choice. The objectives of this study were (a) to evaluate the serum pharmacokinetics of marbofloxacin (5 mg/kg) after intravenous administration in tekes and simulate a multidose regimen; (b) to emulate pharmacokinetic profiles after single dose and steady-state conditions by Monte Carlo simulation (c) to determine the MIC of regional strains of Escherichia coli and Staphylococcus aureus; (d) to perform a PK/PD analysis by Monte Carlo simulation. Pharmacokinetics of marbofloxacin was evaluated in six animals at 3, 10, 24, 50, and 80 days after birth. Marbofloxacin were determined by HPLC. A steady-state multi-dose simulation was carried out, and concentration-time profiles were generated by Monte Carlo simulation. MIC of marbofloxacin against regional E. coli and S. aureus strains were also determined. Finally, a PK/PD analysis was conducted by Monte Carlo simulation. After pharmacokinetic analysis, clearance showed a trend to increase (0.14 and 0.18 L kg-1 hr-1 ), and AUC (36.74 and 15.21 μg hr-1 ml-1 ) and Vss (3.06 and 3.37 L/kg) trended to decrease at 3 and 80 days-old, respectively, showing accumulation ~50% in animals with 3 days. All strains tested of E. coli (MIC90 = 0.06 μg/ml) and S. aureus (MIC90 = 0.25 μg/ml) were susceptible to marbofloxacin. PK/PD analysis suggests that the therapeutic regimen of marbofloxacin could be effective for infections caused by E. coli strains in animals between 3 and 80 days, with a CFR for Cmax /MIC > 10 of 100% and for AUC24 /MIC > 125 of 99.99%; and for infections produced by S. aureus in animals between 3 and 24 days old, with a CFR for Cmax /MIC > 10 of 93.08% and for AUC24 /MIC > 60 of 97.01%, but a higher dose should be used in older animals, because PK/PD endpoints were not met.

The objective of this study was to determine the pharmacokinetic behavior of cefquinome (CFQ) in serum and tissue cage fluid (TCF) in llamas, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration of 2 mg/kg. Two tissue cages (TC) per animal were implanted in the subcutaneous tissue, on the pectoralis major muscles area. Serum and TCF concentrations of CFQ were determined by microbiological assay using Klebsiella pneumoniae ATCC 10031 as the test microorganism. Minimum inhibitory concentrations (MIC) of CFQ against Escherichia coli and Staphylococcus aureus strains isolated from llamas were determined by broth microdilution method. S. aureus ATCC 29213 and E. coli ATCC 25922 strains were used as controls. Finally, a pharmacokinetic/pharmacodynamic (PK/PD) analysis by Monte Carlo simulation, based on pharmacokinetic data obtained from IV, IM and SC administration of CFQ in llamas and MIC values, was carried out to evaluate the antimicrobial efficacy of the dose regimen. CFQ showed a limited distribution, with values of Vdss = 0.10 ± 0.01 and Vz = 0.18 ± 0.04L/kg. Total body clearance (0.05 ± 0.01 L*kg/h) was lower than reported in other species. Absolute bioavailability of IM and SC routes was complete (124 ± 45% and 94 ± 35%, respectively). Moreover, CFQ presented a AUCTCF/AUCserum ratio MIC values, resulting in a better antimicrobial efficacy of CFQ in this biological compartment. MIC90 values for E. coli and S. aureus were 0.06 μg/mL and 0.50 μg/mL, respectively, with a MIC90/MIC50 = 2. Based on the PK/PD analysis, a dose regimen of CFQ of 2 mg/kg q12 h by IV, IM and SC routes, could be effective for the treatment of infections caused by pathogens with MIC values ≤0.50 μg/mL. Therefore, CFQ appears to be a good choice against E. coli and S. aureus in llamas.

The purpose of this study was to determine the pharmacokinetic profile of marbofloxacin in llamas following single IV, IM and SC administration of 5 mg/kg bw. To assess whether these routes could be an option for the administration of marbofloxacin in this specie and estimate efficacy predictors (PK/PD) from bibliographic MIC90 values. The principal pharmacokinetic parameters were Vss = 0.72 ± 0.22 L/kg, Cl = 0.09 ± 0.03 L/kg h (for IV administration), Cmax = 7.43 ± 1.28 μg/mL and 6.94 ± 2.19 μg/mL for IM and SC administration, respectively; t1/2λ = 9.16 ± 1.08 h, 8.47 ± 0.31 h and 6.26 ± 0.87 h and MRT = 7.30 ± 1.07 h, 8.21 ± 1.57 h and 8.27 ± 0.96 h for IV, IM and SC administrations, respectively. The values obtained for the pharmacokinetic parameters were not significantly different among routes of administration except Cmax, Vz and t1/2λ. The values obtained from the PK/PD indices were Cmax/MIC90 (12.4–32.3) and AUC0–24/MIC90 (105.7–178.52 h); taking into account these values, it was concluded that a IM or SC dose of 5 mg/(kg day) of marbofloxacin would be adequate in treating infections caused by susceptible bacteria with MIC